Project Summary/Abstract Next-generation sequencing (NGS) technology has revolutionized the scale and scope of genomic biomedical research. It has made deep whole-genome and whole-transcriptome sequencing feasible, expanding our view of the genome, transcriptome and epigenome. A strong record of discoveries and funding, in addition to some specific geographical and other advantages, now present a number of unique and exciting opportunities to Loma Linda researchers. To make the best use of these opportunities will require access to NGS capabilities. However, there currently exists no NGS instrument at Loma Linda University (LLU). In this application, we are requesting an Illumina NextSeq 500 System, the only desktop NGS system capable of sequencing a human genome with 30 times of coverage in a single run. With the NextSeq 500 System, the genome and transcriptome of any organism can be explored at single-nucleotide resolution without a priori assumptions. Acquisition of this instrument will enhance several NIH-supported research projects at LLU by employing cutting-edge NGS techniques, such as mRNA-seq, miRNA-seq, DNA-seq, genome-seq, reduced representation bisulfite sequencing (RRBS), and ChIP-seq. These LLU investigators carry out a wide range of basic, translational and clinical studies that are designed to elucidate the molecular mechanisms underlying such human diseases as cardiovascular disease, diabetes, cancer, and obesity. Importantly, LLU is situated in the midst of the only Blue Zone (an area with high numbers of centenarians) in the United States, while located within San Bernardino County, a county displaying one of the lowest levels of health and health outcomes nationwide. This puts LLU in a unique and strategic position to discover and address the molecular basis of health, longevity, disease, and health disparities. In recognition of this strategic position, our institution has committed significant resources towards the establishment of a Genomics Center. This creates a direct synergy between the acquisition of the requested NextSeq 500 NGS instrument and the strategic position and mission of our institution. For example, the goal of the Adventist Health Study 2 (AHS2), one of the NIH funded projects listed in this application (PI: Gary Fraser, U01, a Major User), is to correlate the effects of life styles (e.g. diet, exercise, religiosity) with hman diseases (e.g. cancers) and health. Acquisition of a NextSeq 500 NGS System will allow us to view the landscapes of the whole-genome, whole-transcriptome and whole- epigenome and to gain insight on modulation of these landscapes by life style (e.g. diet). Our long-term objective i to provide state-of-the-art genomic tools to: 1) Better understand the molecular mechanisms of human disease and health disparities from a genome-wide approach; 2) Identity novel biomarkers of and novel therapeutic targets for human diseases; and 3) Define the health and life-style profile of the Loma Linda Blue Zone population at the genomic and epigenomic levels.